The human Sirt3 protein deacetylase is exclusively mitochondrial

Helen M. Cooper , Johannes N. Spelbrink (1)

1 Molecular Biology

It has recently been suggested that perhaps as many as 20% of all mitochondrial proteins are regulated through lysine acetylation while Sirt3 has been implicated as an important mitochondrial protein deacetylase. It is therefore of crucial importance that the mitochondrial localization of potential protein deacetylases is unambiguously established. While mouse Sirt3 was recently shown to be mitochondrial, human Sirt3 (HsSirt3) was reported to be both nuclear and mitochondrial and to relocate from the nucleus to the mitochondrion upon cellular stress. We show here using various HsSirt3 expression constructs and a combination of immunofluorescence and careful subcellular fractionation that in contrast to the earlier report human Sirt3 is exclusively mitochondrial. We discuss possible experimental explanations for these discrepancies. In addition, we suggest on the basis of the analysis of public genome databases that the full-length mouse Sirt3 protein is a 37 kDa mitochondrial precursor protein contrary to the previously suggested 29 kDa protein.

Mots clés: Life Sciences

Helen M. Cooper, Johannes N. Spelbrink. The human Sirt3 protein deacetylase is exclusively mitochondrial. Biochemical Journal, 2008, 411 (2), pp.279-285. ⟨10.1042/BJ20071624⟩. ⟨hal-00478931⟩